Losing without Fighting - Simple Aversive Stimulation Induces Submissiveness Typical for Social Defeat via the Action of Nitric Oxide, but Only When Preceded by an Aggression Priming Stimulus

Abstract

Losing a fight (social defeat) induces submissiveness and behavioral depression in many animals, but the mechanisms are unclear. Here we investigate how the social defeat syndrome can be established as a result of experiencing aversive stimuli and the roles of neuromodulators in the process. While biogenic amines and nitric oxide (NO) are associated with reduced aggression in mammals and insects, their specific actions during conflict are unknown. Although the social defeat syndrome normally results from complex interactions, we could induce it in male crickets simply by applying aversive stimuli (AS) in an aggressive context. Aggressive crickets became immediately submissive and behaved like losers after experiencing two brief AS (light wind puffs to the cerci), but only when preceded by a priming stimulus (PS, stroking the antenna with another male antenna). Notably, submissiveness was not induced when the PS preceded the AS by more than 1 min, or when the PS followed the AS, or using a female antenna as the preceding stimulus. These findings suggest that any potentially detrimental stimulus can acquire the attribute of an aversive agonistic signal when experienced in an aggressive context. Crickets, it seems, need only to evaluate their net sensory impact rather than the qualities of a variety of complex agonistic signals. Selective drug treatments revealed that NO, but not serotonin, dopamine or octopamine, is necessary to establish the submissive status following pairing of the priming and aversive stimuli. Moreover, treatment with an NO donor also induced the social defeat syndrome, but only when combined with the PS. This confirms our hypothesis that aversive agonistic experiences accumulated by crickets during fighting invoke social defeat via the action of NO and illustrates that a relatively simple mechanism underlies the seemingly complex social decision to flee. The simple stimulus regime described here for inducing social defeat opens new avenues for investigating the cellular control of subordinate behavior and post-conflict depression.

Serotonin Mediates Depression of Aggression After Acute and Chronic Social Defeat Stress in a Model Insect

“…An alternative, or at least complementary possibility, is that the action of 5HT in losers depends on prior activation of the neurotransmitter pathway that controls the initial decision to retreat. In crickets, the decision to flee and subsequent loser depression is initiated by nitric oxide (NO) and does not require 5HT (Stevenson and Rillich, 2015 ; Rillich and Stevenson, 2017 ). Here we showed that blocking NO synthesis with LNAME either before (Figure 3B ) or after (Figure 4 ) multiple defeats prohibited long term aggressive depression even more effectively than ketanserin.…”

“…That used for AMTP has been shown to be the minimum required to achieve almost complete depletion of serotonin as determined by immunocytochemistry, but above that shown to achieve complete depletion as determined by HPLC (see Stevenson et al, 2000 ). The dosages for all other drugs were selected as the minimum that induced clear effects on aggression, without obvious detrimental effect on general motility as judged by eye and were established in previous investigations (Rillich and Stevenson, 2014 , 2015 , 2017 ; Stevenson and Rillich, 2015 ), or in pilot experiments for the present study (Figure S1 ).…”

“…It has thus been suggested that “behavioral features of dominant male crickets are likely to be connected with the activation of the serotonergic system” whereas “a decrease in serotonergic activity may be functionally important for the control of loser behavior” (Dyakonova and Krushinsky, 2013 ). More recently, it was found in crickets that nitric oxide (NO) triggers the actual decision to flee and establishes subsequent loser depression (Stevenson and Rillich, 2015 ; Rillich and Stevenson, 2017 ), whereas octopamine and dopamine (OA, DA, Stevenson et al, 2005 ; Rillich and Stevenson, 2014 ) promote recovery. In view of this, we also test how drugs that influence these neuromodulators influence aggression after chronic social defeat in comparison to serotonergic drugs.…”

Descending and Ascending Signals That Maintain Rhythmic Walking Pattern in Crickets

“…This study focuses on cricket locomotion. Cricket is one of the ideal experimental animals to investigate neuronal mechanisms underlying varieties of behaviors such as locomotion [walking (Owaki et al, 2021 ), flight (Schul and Schulze, 2001 ; Pollack and Martins, 2007 ), swimming (Matsuura et al, 2002 ), aggressive behavior (Stevenson et al, 2000 ; Sakura et al, 2012 ; Rillich and Stevenson, 2014 , 2017 ), escape behavior (Jacobs et al, 2008 ; Yono and Aonuma, 2008 ), mating behavior (Nagao et al, 1991 ; Ureshi et al, 2002 ; Nagamoto et al, 2005 ; Killian et al, 2006 ), learning and memory (Matsumoto et al, 2006 ), phonotaxis (Baden and Hedwig, 2008 ; Pollack and Kim, 2013 ), circadian rhythm (Saifullah and Tomioka, 2002 ) and so on]. On the other hand, in the robotics field, cricket inspired robots are made where design and control law of autonomous robots are investigated [the locomotion of micro-cricket robot: (Birch et al, 2000 ), phonotaxis robot: (Lund et al, 1997 ; Reeve et al, 2005 ), group behavior: (Funato et al, 2008 , 2011 ), cricket-robot interaction: (Guerra et al, 2010 ; Kawabata et al, 2013a , Kawabata et al, 2013b )].…”